title: Three-dimensional telomere dynamics in follicular thyroid cancer.
abstract: BACKGROUND
  Over the last decade, annual incidence rates for thyroid cancer have been among the highest of all cancers in the Western world. However, the genomic mechanisms impacting thyroid carcinogenesis remain elusive.
  
  
  METHODS
  We employed an established mouse model of follicular thyroid cancer (FTC) with a homozygous proline to valine mutation (Thrb(PV/PV)) in the thyroid receptor β1 (TRβ1) and applied quantitative three-dimensional (3D) telomere analysis to determine 3D telomeric profiles in Thrb(PV)(/PV), Thrb(PV/)(+), and Thrb(+/+) mouse thyrocytes before and after histological presentation of FTC.
  
  
  RESULTS
  Using quantitative fluorescent in situ hybridization (Q-FISH) and TeloView™ image analysis, we found altered telomeric signatures specifically in mutant mouse thyrocytes. As early as 1 month of age, Thrb(PV/PV) mouse thyrocytes showed more telomeres than normal and heterozygous age-matched counterparts. Importantly, at the very early age of 1 month, 3D telomeric profiles of Thrb(PV/PV) thyrocyte nuclei reveal genetic heterogeneity with several nuclei populations exhibiting different telomere numbers, suggestive of various degrees of aneuploidy within the same animal. This was detected exclusively in Thrb(PV/PV) mice well before the presentation of histological signs of thyroid carcinoma.
  
  
  CONCLUSIONS
  We identified quantitative 3D telomere analysis as a novel tool for early detection and monitoring of thyrocyte chromosomal (in)stability. This technique has the potential to identify human patients at risk for developing thyroid carcinoma.
authors.affiliation: 1 Department of Human Anatomy & Cell Science, Faculty of Medicine, University of Manitoba , Winnipeg, Canada .
authors.forename: Landon
authors.initials: L
authors.lastname: Wark
authors.forename: Adrian
authors.initials: A
authors.lastname: Danescu
authors.forename: Suchitra
authors.initials: S
authors.lastname: Natarajan
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zhu
authors.forename: Sheue-yann
authors.initials: SY
authors.lastname: Cheng
authors.forename: Sabine
authors.initials: S
authors.lastname: Hombach-Klonisch
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D016615:Telomere / Q000737:chemistry*; D013961:Thyroid Gland / Q000166:cytology / Q000473:pathology; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*
chemical_list: D037042:Thyroid Hormone Receptors beta